Red wine is a well-known alcoholic beverage, and is known to have phenolic compounds (PCs), which contribute to its antioxidant activity and have other beneficial advantages for human health. The aim of this study was to evaluate the effect of the simulated gastro-intestinal digestion and the Caco-2 transepithelial transport assay on the PCs, bioavailability, and the antioxidant capacity of red wines. The contents of PCs in red wine were significantly reduced during most of the digestion phases. Phenolic acid had the greatest permeability, while the flavonols had the weakest. The bioavailability of PCs ranged from 2.08 to 24.01%. The result of the partial least squares structural equation model showed that the three phenols were positively correlated with the antioxidant activity of red wine. The contribution of anthocyanins was the largest (0.8667).